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Altered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic mice

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dc.contributor.authorHayashi, Mansuo L-
dc.contributor.authorChoi, Se-Young-
dc.contributor.authorRao, B.S.Shankaranarayana-
dc.contributor.authorJung, Hae-Yoon-
dc.contributor.authorLee, Hey-Kyoung-
dc.contributor.authorZhang, Dawei-
dc.contributor.authorChattarji, Sumantra-
dc.contributor.authorKirkwood, Alfredo-
dc.contributor.authorTonegawa, Susumu-
dc.date.accessioned2010-09-12T22:57:51Z-
dc.date.available2010-09-12T22:57:51Z-
dc.date.issued2004-06-
dc.identifier.citationNeuron 42, 773-787en
dc.identifier.issn0896-6273-
dc.identifier.urihttps://hdl.handle.net/10371/69797-
dc.description.abstractMolecular and cellular mechanisms for memory consolidation in the cortex are poorly known. To study the relationships between synaptic structure and function in the cortex and consolidation of long-term memory, we have generated transgenic mice in which catalytic activity of PAK, a critical regulator of actin remodeling, is inhibited in the postnatal forebrain. Cortical neurons in these mice displayed fewer dendritic spines and an increased proportion of larger synapses compared to wild-type controls. These alterations in basal synaptic morphology correlated with enhanced mean synaptic strength and impaired bidirectional synaptic modifiability (enhanced LTP and reduced LTD) in the cortex. By contrast, spine morphology and synaptic plasticity were normal in the hippocampus of these mice. Importantly, these mice exhibited specific deficits in the consolidation phase of hippocampus-dependent memory. Thus, our results provide evidence for critical relationships between synaptic morphology and bidirectional modifiability of synaptic strength in the cortex and consolidation of long-term memory.en
dc.description.sponsorshipWe are grateful of Xiaoning Zhou, Wenjiang Yu, Frank Bushard, and Jayson Derwin for excellent technical assistance. We thank Drs. David Gerber, Thomas McHugh, Matthew Anderson, Audrey Chang, Yasunori Hayashi, Guo-song Liu, Morgan Sheng, and Mark Bear for critical discussions; many members of the Tonegawa lab for helpful advice; Dr. Tsuyoshi Miyakawa for advice on behavioral experi-
ments; Marcia Feinberg, Maria Ericsson, Elizabeth Benecchi, and
Dr. Kristen Harris for help on electron microscopy. This study was
supported by NIH, HHMI, and RIKEN (S.T.) and NIH (A.K.).
en
dc.language.isoenen
dc.publisherElsevieren
dc.titleAltered cortical synaptic morphology and impaired memory consolidation in forebrain-specific dominant-negative PAK transgenic miceen
dc.typeArticleen
dc.contributor.AlternativeAuthor정해윤-
dc.contributor.AlternativeAuthor최세영-
dc.contributor.AlternativeAuthor이혜경-
dc.identifier.doi10.1016/j.neuron.2004.05.003-
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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